Calmodulin is thought to be the most important calcium sensor in signal transduction. When the four calcium binding sites on calmodulin are occupies, calmodulin becomes a multifunctional activator that regulates a large number of critical cell functions, particularly in neurons of the central nervous system. However, little is known about how the large number of calmodulin-dependent cell functions can be selectively controlled. In the proposed experiments, I will define the fundamental mechanisms by which calmodulin availability is regulated in space and time and investigate the importance of this local calmodulin regulation for CaM kinaseII function. These studies will be carried out in living cultured hippocampal neurons.